根據(jù)NEOSPHERE和TRYPHAENA研究的病理完全緩解增加，2012年美國食品藥品管理局批準（注：中國至今尚未批準）帕妥珠單抗用于HER2陽性局部乳腺癌新輔助治療,。這些研究證實THP（多西他賽＋曲妥珠單抗＋帕妥珠單抗）與TH相比、FEC→THP（氟尿嘧啶＋表柔比星＋環(huán)磷酰胺→THP）與FEC→TH相比,、TCHP（多西他賽＋卡鉑＋曲妥珠單抗＋帕妥珠單抗）與TCH相比,，病理完全緩解率顯著提高。不過,，在美國,，雖然AC（多柔比星＋環(huán)磷酰胺）比FEC更受歡迎，但是缺少AC→THP,、AC→TH,、TCHP之間的新輔助治療數(shù)據(jù)比較。

　　2018年9月15日,，施普林格·自然旗下《乳腺癌研究與治療》在線發(fā)表美國哈佛大學醫(yī)學院麻省總醫(yī)院癌癥中心的研究報告,，對AC→TH±帕妥珠單抗新輔助治療局部HER2陽性乳腺癌患者的有效性和耐受性進行了比較。

　　該研究對2011～2016年美國哈佛大學醫(yī)學院麻省總醫(yī)院癌癥中心（大型學術(shù)型醫(yī)療機構(gòu)）和兩家附屬社區(qū)醫(yī)院121例1～3期HER2陽性乳腺癌患者接受帕妥珠單抗新輔助治療或劑量密集AC→TH治療的臨床病理特征進行回顧,。病理完全緩解定義為術(shù)前新輔助治療后病理檢查腫瘤消失或未浸潤（ypT0/is）且淋巴結(jié)未轉(zhuǎn)移（ypN0）,。通過費希爾精確檢驗和邏輯回歸模型，進行統(tǒng)計學分析,。

　　結(jié)果發(fā)現(xiàn),，有,、無帕妥珠單抗的方案相比，病理完全緩解率較高：

• TCHP：63%

• 劑量密集AC→THP：60%

• THP：55%

• 劑量密集AC→TH：46%

　　THP與其他方案相比,，毒性所致周期延遲顯著較少（P=0.02）,、劑量減少最少、住院率最低,、治療停止率最低,。

　　因此，根據(jù)該研究結(jié)果,，對于HER2陽性局部乳腺癌患者,，有帕妥珠單抗的治療方案（包括THP）與劑量密集AC→TH相比，病理完全緩解率較高,，其中THP方案的耐受性最佳,。由于新輔助治療方案不同，需要進一步研究確定最佳治療順序和升級或降級策略,，對HER2陽性局部乳腺癌的新輔助治療方案進行個體化,。

Breast Cancer Res Treat. 2018 Sep 15.

Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer.

Laura Spring, Andrzej Niemierko, Stephanie Haddad, Megan Yuen, Amy Comander, Kerry Reynolds, Jennifer Shin, Atul Bahn, Elena Brachtel, Michelle Specht, Barbara L. Smith, Alphonse Taghian, Rachel Jimenez, Jeffrey Peppercorn, Steven J. Isakoff, Beverly Moy, Aditya Bardia.

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, USA.

PURPOSE: Based on improvement in pathologic complete response (pCR) in the NeoSphere and TRYPHAENA studies, the FDA approved neoadjuvant pertuzumab for HER2+ localized breast cancer. These studies demonstrated high pCR rates with THP (docetaxel + HP), FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-THP, and TCHP (docetaxel, carboplatin + HP). However, in the United States, doxorubicin/cyclophosphamide (AC) is favored over FEC despite no data comparing neoadjuvant AC-THP with AC-TH or TCHP. Here we report outcomes for patients with localized HER2+ breast cancer treated with pertuzumab-containing neoadjuvant regimens and AC-TH.

METHODS: We reviewed clinicopathological characteristics of patients with HER2+ breast cancer (Stage I-III) treated with either a neoadjuvant pertuzumab-containing regimen or dose-dense (dd) AC-TH, from 2011 to 2016 at a large academic medical institution and two affiliated community sites. pCR was defined as ypT0/is ypN0. Fisher's exact test and logistic regression analysis were used for statistical analysis.

RESULTS: In this study (N = 121), pCR was numerically higher with pertuzumab-based regimens, including ddAC-THP (60%), TCHP (63%), THP (55%), as compared with ddAC-TH (46%). THP resulted in significantly less cycle delays due to toxicity compared to the other regimens (p = 0.02). THP also resulted in the least dose reductions, lowest rate of hospitalization, and lowest rate of treatment discontinuation.

CONCLUSIONS: Pertuzumab-based regimens, including THP, resulted in higher pCR rates as compared to ddAC-TH, with the THP regimen associated with the best tolerability among patients with localized HER2+ breast cancer. Given the various neoadjuvant regimens, additional studies are needed to determine optimal treatment sequencing and escalation/de-escalation strategies to personalize neoadjuvant regimens for localized HER2+ breast cancer.

KEYWORDS: Neoadjuvant HER2 Pathologic complete response Pertuzumab Trastuzumab

DOI: 10.1007/s10549-018-4959-8